1. Field
The present disclosure relates to a polypeptide based block copolymer having biodegradability due to peptidase, and a process for the preparation thereof, and polymer micelles using the same.
2. Description of Related Art
Micelles generally refer to a thermostable and uniform spherical structure formed by low-molecular weight materials having amphiphilicity, that is, having a hydrophilic group and a hydrophobic group at the same time. When an insoluble drug is dissolved in and introduced to a compound having the micelle structure, the drug is present inside the micelles, and these micelles can have high applicability as a carrier for drug delivery since these micelles can perform target-oriented drug release in the body responding to changes in temperature and pH.
Korean Patent Application No. 10-2001-0035265 discloses a preparation of micelles using a polyethylene glycol and a biodegradable polymer. These materials have advantages in that they all have bioaffinity due to their biodegradability, however, they have disadvantages in that drug delivery in a target area is difficult since these materials are not sensitive to changes in the body, for example, specific changes such as pH changes.
In addition, Korean Patent Application No. 10-2010-0112491 discloses a preparation of micelles using a block copolymer of a poly(β-aminoester) compound and a polyethylene glycol-based compound. These materials have advantages in that they are sensitive to specific changes such as pH changes, however, they have disadvantages in that the control of degradation rate is impossible since degradation occurs due to hydrolysis after dimicellization.
Meanwhile, the pH environment in a body generally indicates pH 7.4 to 7.2, however, it has been known that peripheral pH of abnormal cells such as cancer cells indicates pH 3.0 to 7.0, which is slightly acidic to strongly acidic. Recently, studies have been carried out in which a drug is released at pH 7.0 or lower in order to specifically deliver the drug to cancer cells.
U.S. Pat. No. 5,955,509 having the tile of “pH dependent polymer micelles” discloses a method for preparing pH-sensitive polymer micelles in which a block copolymer of poly(vinyl N-heterocycle) and poly(alkylene oxide) forms micelles at pH 6.0 or higher, and the block copolymer is collapsed between pH 2 and 6, and Japanese Patent Application Laid-Open Publication No. 2002-179556 having the tile of “block copolymer-anti-cancer drug complex medicine” discloses a block copolymer of a hydrophilic polyethylene glycol-based compound and a hydrophobic polyamino acid-based compound forming micelles at a specific pH.
In view of the above, the inventors identified that, when a pH-sensitive block copolymer formed from a polyethylene glycol-based compound and a polyglutamic acid-based compound including a tertiary amine group is used, micelles are collapsed and thereby drugs can be released when pH is 7.0 or less, and micelles are formed and collapsed by the pH difference of 0.2, therefore, the pH-sensitive block copolymer has both pH sensitivity and biodegradability due to peptidase, and thereby control of the degradation rate relating to drug release cycle is possible and the biotoxicity of the residues after degradation can be reduced, thereby completing the present disclosure.